DESCRIPTION

Aminohippurate sodium is an agent to measure effective renal plasma flow (ERPF).
It is the sodium salt of para-aminohippuric acid, commonly abbreviated "PAH".
It is water soluble, lipid-insoluble, and has a pKa of 3.83. The empirical formula
of the anhydrous salt is C9H9N2NaO3
and its structural formula is:

It is provided as a sterile, non-preserved 20 percent aqueous solution for injection, with a pH of 6.7 to 7.6. Each 10 mL contains: Aminohippurate sodium (aminohippurate) 2 g. Inactive ingredients: Sodium hydroxide to adjust pH, water for injection, q.s.

INDICATIONS

Measurement of the functional capacity of the renal tubular secretory mechanism.

DOSAGE AND ADMINISTRATION

For intravenous use only

Clearance measurements using single injection techniques are generally inaccurate,
particularly in the measurement of ERPF. For this reason, intravenous infusions
at fixed rates are used to sustain the plasma PAH concentration at the desired
level.

To measure ERPF, the concentration of PAH in the plasma should be maintained
at 2 mg per 100 mL, which can be achieved with a priming dose of 6 to 10 mg/kg
and an infusion dose of 10 to 24 mg/min.

As a research procedure for the measurement of TmPAH, the plasma
level of PAH must be sufficient to saturate the capacity of the tubular secretory
cells. Concentrations from 40 to 60 mg per 100 mL are usually necessary.

Technical details of these tests may be found in Smith1; Wesson2;
Bauer3; Pitts4; and Schnurr5.

Parenteral drug products should be inspected visually for particulate matter
and discoloration prior to use, whenever solution and container permit.

NOTE: The normal color range for this product is a colorless to yellow/brown
solution. The efficacy is not affected by color changes within this range.

Calculations

Effective Renal Plasma Flow (ERPF)

The clearance of PAH, which is extracted almost completely from the plasma during its passage through the renal circulation, constitutes a measure of ERPF. Hence:

The value of the expression UPAHV, used in calculations of ERPF
and TmPAH, may be found by determining the amount of PAH in a measured
volume of urine excreted within a specific period of time.

These calculations are based on a body surface area of 1.73 m2.
Corrections for variations in surface area are made by multiplying the values
obtained for ERPF and TmPAH by 1.73/A, where A is the subject surface area.

REFERENCES

1. Smith, H.W.: Lectures on the kidney, University Extension Division, University
of Kansas, Lawrence, Kansas, 1943.

SIDE EFFECTS

Hypersensitivity reactions including anaphylaxis, angioedema, urticaria, vasomotor disturbances, flushing, tingling, nausea, vomiting, and cramps may occur. Patients may have a sensation of warmth or the desire to defecate or urinate during or shortly following initiation of infusion.

DRUG INTERACTIONS

Renal clearance measurements of PAH cannot be made with any significant accuracy
in patients receiving sulfonamides, procaine, or thiazolesulfone. These compounds
interfere with chemical color development essential to the analytical procedures.

PRECAUTIONS

General

For measurement of ERPF, small doses of PAH are used. However, in research
procedures to measure TmPAH, high plasma levels are required to saturate
the capacity of the tubular cells. During these procedures, the intravenous
administration of PAH solutions should be carried out slowly and with caution.
The patient should be continuously observed for any adverse reactions.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been done to evaluate any effects upon fertility or carcinogenic potential of PAH.

Pregnancy

Pregnancy Category C. Animal reproduction studies have not been done
with PAH. It is also not known whether PAH can cause fetal harm when given to
a pregnant woman or can affect reproduction capacity. PAH should be given to
a pregnant woman only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when PAH is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of PAH did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

CONTRAINDICATIONS

CLINICAL PHARMACOLOGY

PAH is filtered by the glomeruli and is actively secreted by the proximal tubules.
At low plasma concentrations (1.0 to 2.0 mg/100 mL), an average of 90 percent
of PAH is cleared by the kidneys from the renal blood stream in a single circulation.
It is ideally suited for measurement of ERPF since it has a high clearance,
is essentially nontoxic at the plasma concentrations reached with recommended
doses, and its analytical determination is relatively simple and accurate.

PAH is also used to measure the functional capacity of the renal tubular secretory
mechanism or transport maximum (TmPAH). This is accomplished by elevating
the plasma concentration to levels (40-60 mg/100 mL) sufficient to saturate
the maximal capacity of the tubular cells to secrete PAH.

Inulin clearance is generally measured during TmPAH determinations since glomerular
filtration rate (GFR) must be known before calculations of secretory Tm measurements
can be done (see DOSAGE AND ADMINISTRATION, Calculations).